title: Regulation of dendritic filopodial interactions by ZO-1 and implications for dendrite morphogenesis.
abstract: Neuronal dendrites dynamically protrude many fine filopodia in the early stages of neuronal development and gradually establish complex structures. The importance of the dendritic filopodia in the formation of axo-dendritic connections is established, but their role in dendrite morphogenesis remains unknown. Using time-lapse imaging of cultured rat hippocampal neurons, we revealed here that many filopodia dynamically protruded from dendrites and transiently interacted with each other to form dendritic filopodia-filopodia contacts in the early stages of neuronal development. The MAGUK family member, Zonula Occludens-1 (ZO-1), which is known to be associated with the nectin and cadherin cell adhesion systems, was concentrated at these dendritic filopodia-filopodia contact sites and also at the tips of free dendritic filopodia. Overexpression of ZO-1 increased the formation of dendritic filopodia and their interactions, and induced abnormal dendrite morphology. Conversely, knockdown of ZO-1 decreased the formation of dendritic filopodia and their interactions, and induced abnormal dendrite morphology which was different from that induced by the overexpression of ZO-1. The components of the nectin and cadherin systems were co-localized with ZO-1 at the dendritic filopodia-filopodia contact sites, but not at the tips of free dendritic filopodia. Overexpression of ZO-1 increased the accumulation of these cell adhesive components at the dendritic filopodia-filopodia contact sites and stabilized their interactions, whereas knockdown of ZO-1 reduced their accumulation at the dendritic filopodia-filopodia contact sites. These results indicate that ZO-1 regulates dendritic filopodial dynamics, which is implicated in dendrite morphogenesis cooperatively with the nectin and cadherin systems in cultured neurons.
authors.affiliation: Division of Molecular and Cellular Biology, Department of Biochemistry and Molecular Biology, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Ryouhei
authors.initials: R
authors.lastname: Komaki
authors.forename: Hideru
authors.initials: H
authors.lastname: Togashi
authors.forename: Yoshimi
authors.initials: Y
authors.lastname: Takai
mesh_terms: D000818:Animals; D015820:Cadherins / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002478:Cells, Cultured; D003712:Dendrites / Q000378:metabolism*; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D000075983:Nectins; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D011485:Protein Binding; D021381:Protein Transport; D011554:Pseudopodia / Q000378:metabolism*; D017966:Pyramidal Cells / Q000166:cytology / Q000378:metabolism; D051381:Rats; D013569:Synapses / Q000378:metabolism; D062826:Zonula Occludens-1 Protein / Q000235:genetics / Q000378:metabolism*
chemical_list: D015820:Cadherins; D015815:Cell Adhesion Molecules; D000075983:Nectins; D062826:Zonula Occludens-1 Protein